The Candidate, Robert A. Burger, is an academic gynecologic oncologist who will establish a research career devoted to developmental therapeutics of epithelial ovarian cancer (EOC). The 25 percent overall survival for patients with EOC has been attributed to advanced stage at diagnosis and limitations of primary therapy. Angiogenesis plays a central role in ovarian cancer progression, allowing one to exploit this process in the development of effective treatment strategies. Dr. Burger s overall hypothesis is that inhibition of tumor angiogenesis in ovarian cancer will decrease metastatic behavior of this disease, in turn improving survival. His secondary hypothesis is that intermediate endpoint biomarkers (IEBs) within tumor tissue and serum, and information derived from dynamic magnetic resonance imaging (MRI), will be useful tools in predicting and tracking response to novel angiogenesis inhibitors. Dr. Burger will work with an immunocompetent, syngeneic EOC tumor model in the Fischer 344 rat, which should allow direct translation of pre-clinical results to human application. This model, utilizing NuTu-19 rat EOC cells, is parallel to the human disease in its histopathologic features, pattern of spread and tumorigenicity. Under the guidance of his proposed sponsors at UCI, Dr. Burger aims to examine the impact of anti-sense vascular endothelial growth factor (VEGF) gene transfection, anti-VEGF monoclonal antibody administration, as well as treatment with SU5416 and SU6668, specific VEGF receptor antagonists, on disease control within the NuTu-19 model. He then plans to translate this information into the development of phase II studies in patients with advanced, recurrent EOC. In order to accomplish the training necessary to conduct this line of patient-oriented translational research, Dr. Burger will complete a curriculum of graduate course work in molecular biology, pharmacology, and clinical trials conduct. He will also attend extramural scientific symposia, in which he will not only gain important information related to his field of career development, but will also present his findings for peer review. Finally, Dr. Burger will generate a logical sequence of original publications and extramural funding specific to the proposed work.